Adenylate cyclase in rat liver plasma membranes has been solubilized with the use of detergents. Procedures have been developed for assaying the binding of radioactive Gpp(NH)p and glucagon to various fractions obtained after detergent solubilization of membranes and subsequent chromatography. It is concluded that most of the guanine nucleotide binding sites are not associated with purified adenylate cyclase; the purified enzyme is activated by Gpp(NH)p indicating that the guanine nucleotide regulatory component remains associated with adenylate cyclase during purification. The purified enzyme is activated by glucagon. However, a crude solubilized fraction can be restored partially to a glucagon-sensitive state after removal of detergents by dialysis. These findings indicate that coupling of the glucagon receptor to the detergent dispersed adenylate cyclase system can be re-constituted. The role of membrane lipids in the reconstitution process is being investigated.